fosgonimeton (ATH-1017) / Athira Pharma - LARVOL DELTA

Open Label Study of ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=423 | Terminated | Sponsor: Athira Pharma | Completed ➔ Terminated; ATH-1017-AD-0203 was terminated after the Ph2/3 parent trial (LIFT-AD; NCT04488419) did not meet its primary endpoint, the GST score.

Trial termination • Alzheimer's Disease • CNS Disorders

ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies (SHAPE Trial) (clinicaltrials.gov) - P2 | N=28 | Terminated | Sponsor: Athira Pharma | Completed ➔ Terminated; Enrollment ended early due to study design limitations.

Trial termination • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Athira Pharma Reports Full Year 2024 Financial Results and Pipeline and Business Updates (GlobeNewswire) - "ATH-1105: The study was completed in November 2024 and evaluated the safety and tolerability of ATH-1105 and included measurements of pharmacokinetic outcomes...Athira is on track to enable dosing ALS patients in 2025....Additionally, Athira paused further development of fosgonimeton, including the related open label extension clinical trial, while continuing the development of ATH-1105 and exploring partnering options."

Discontinued • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis

Drug Development. (PubMed, Alzheimers Dement) - "The data presented demonstrate the ability of fosgonimeton to potentially address autophagic impairment in AD, which may have important implications regarding the attenuation of pTau pathology. These effects of fosgonimeton, in addition to the neurotrophic and neuroprotective effects previously demonstrated in preclinical models, highlight the therapeutic potential of the HGF system for neurodegenerative disorders, wherein autophagic impairment is a key pathological hallmark."

Journal • Alzheimer's Disease • CNS Disorders • BECN1 • HGF • LAMP2

Drug Development. (PubMed, Alzheimers Dement) - P2/3 | "This study provides preliminary evidence that, on a cellular level, the neuroprotective ability of fosgonimeton against Aβ-mediated toxicity in primary neurons is maintained in the presence of lecanemab. Furthermore, in some conditions, only the combination of fosgo-AM and lecanemab demonstrated a significant increase in neuronal survival. While additional experiments are required to characterize these effects, these initial observations may have important implications regarding the potential of fosgonimeton as a treatment for AD, with or without Aβ-targeting antibodies."

Journal • Alzheimer's Disease • CNS Disorders • HGF

LIFT-AD: ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=554 | Completed | Sponsor: Athira Pharma | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Open Label Study of ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=423 | Completed | Sponsor: Athira Pharma | Trial primary completion date: Aug 2028 ➔ Oct 2024 | Active, not recruiting ➔ Completed | Trial completion date: Sep 2028 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Athira Pharma to Present Results from Phase 2/3 LIFT-AD Clinical Trial of Fosgonimeton at the Clinical Trials on Alzheimer’s Disease (CTAD) 2024 Meeting (GlobeNewswire) - "As previously reported, topline results from the LIFT-AD trial did not achieve statistical significance for the primary endpoint of the Global Statistical Test (GST) nor its key secondary endpoints compared with placebo at 26 weeks. However, both components of GST, cognition (ADAS-Cog11) and function (ADCS-ADL23), directionally favored fosgonimeton treatment, and in pre-specified subgroups characterized by more rapid disease progression (moderate AD and APOE4 carriers), cognition and function improved or stabilized in the fosgonimeton treated group...Athira is focused on advancing the clinical development program for ATH-1105...Athira completed the first cohort of healthy volunteers in June 2024 and expects to complete the full study by year-end 2024, with a goal to begin dosing ALS patients in 2025."

P2/3 data • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

Fosgonimeton for the Treatment of Alzheimer's Disease; Efficacy and Safety Results from the LIFT-AD Trial (CTAD 2024) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders

Athira Pharma Announces Topline Results from Phase 2/3 LIFT-AD Clinical Trial of Fosgonimeton for Mild-to-Moderate Alzheimer’s Disease (GlobeNewswire) - P2/3 | N=554 | LIFT-AD (NCT04488419) | Sponsor: Athira Pharma | "A -0.08 change in GST favoring fosgonimeton that did not reach statistical significance (p=0.70); The change in cognition from baseline as assessed by ADAS-Cog11...was -0.39 for the placebo group and -1.09 for the fosgonimeton treated group...In the fosgonimeton treated group, there was an increase (improvement) of 0.65 in function as measured by ADCS-ADL23 versus a decline of -0.02 in placebo...The change in cognition from baseline as assessed by ADAS-Cog11 in moderate AD patients...showed the fosgonimeton treatment group (n=61) improved compared to placebo (n=70), with a delta of -1.16 (p=0.39)."

P2/3 data • Alzheimer's Disease • CNS Disorders

Athira Pharma Presents Preclinical Data Demonstrating New Insights into the Mechanism by Which Fosgonimeton Protects Neurons from Alzheimer’s Disease-Related Pathology at the Alzheimer’s Association International Conference (AAIC) 2024 (GlobeNewswire) - "Athira Pharma, Inc...presented new preclinical data further highlighting the therapeutic potential of fosgonimeton at the Alzheimer’s Association International Conference (AAIC) 2024, being held in Philadelphia from July 28-Aug. 1, 2024....Fosgonimeton can mitigate amyloid-β-induced disruption of autophagy, an essential cellular process that plays a key role in the removal of pathological proteins, such as pTau, and is known to be impaired in Alzheimer’s disease....Fosgonimeton is neuroprotective against amyloid-beta-mediated toxicity in primary neurons, either alone or in combination with lecanemab, and, in some conditions, the combination of fosgonimeton and lecanemab led to numerically higher levels of neuroprotection....The data support the continued investigation of fosgonimeton and Aβ-mAbs as a potential combination therapy for the treatment of Alzheimer’s disease."

Preclinical • Alzheimer's Disease • CNS Disorders

Open Label Study of ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=450 | Active, not recruiting | Sponsor: Athira Pharma | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Feb 2027 ➔ Sep 2028 | Trial primary completion date: Jan 2027 ➔ Aug 2028

Enrollment closed • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Athira Pharma Announces Last Patient Completed LIFT-AD Clinical Trial of Fosgonimeton in Mild-to-Moderate Alzheimer’s Disease (GlobeNewswire) - "Athira Pharma...announced the completion of dosing for the last patient in the Phase 2/3 LIFT-AD clinical trial evaluating fosgonimeton in people with mild-to-moderate Alzheimer’s disease (AD). The Company is now targeting to report topline results from the LIFT-AD trial by the end of the third quarter of 2024 and has been invited to discuss the fuller data set during an oral presentation on October 29, 2024, at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference taking place from October 29 - November 1, 2024, in Madrid, Spain."

P2/3 data • Trial status • Alzheimer's Disease

Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics. (PubMed, PCN Rep) - "The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments...The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients."

Journal • P3 data • Alzheimer's Disease • CNS Disorders • Dementia

Fosgonimeton attenuates amyloid-β-induced autophagic impairments in primary cortical neurons (AAIC 2024) - "The data presented demonstrate the ability of fosgonimeton to potentially address autophagic impairment in AD, which may have important implications regarding the attenuation of pTau pathology . These effects of fosgonimeton, in addition to the neurotrophic and neuroprotective effects previously demonstrated in preclinical models , highlight the therapeutic potential of the HGF system for neurodegenerative disorders, where in autophagic impairment is a key pathological hallmark ."

Alzheimer's Disease • CNS Disorders • BECN1 • HGF • LAMP2

Neuroprotective effects of fosgonimeton and amyloid-β-targeting monoclonal antibodies against amyloid-β toxicity in primary neuron culture (AAIC 2024) - P2/3 | "This study provides preliminary evidence that, on a cellular level, the neuroprotective ability of fosgonimeton against A β -mediated toxicity in primary neurons is maintained in the presence of lecanemab . Furthermore, in some conditions, only the combination of fosgo-AM and lecanemab demonstrated a significant increase in neuron al survival. While additional experiments are required to characterize these effects, these initial observations may have important implications regarding the potential of fosgonimeton as a treatment for AD, with or without Aβ-targeting antibodies ."

Alzheimer's Disease • CNS Disorders • HGF

Athira to Host Webinar Highlighting Potential for Fosgonimeton to Protect and Preserve Neuronal Health in Mild-to-Moderate Alzheimer’s Disease Patients (GlobeNewswire) - Athira Pharma, Inc...today announced that it will host a webinar event with key opinion leaders to discuss the unmet medical need and the potential opportunity for fosgonimeton to improve cognition and function in mild-to-moderate Alzheimer’s disease. The event titled, 'Lead Up to LIFT-AD Readout: Understanding the Primary Endpoint and Continued Need for Effective New Treatments in Alzheimer’s Disease,' will take place on Tuesday, June 18th, 2024, beginning at 11:30 a.m. ET....'Additionally, we will provide an overview of the Phase 2/3 LIFT-AD trial and review the relevance of the trial’s primary endpoint, the Global Statistical Test (GST), a combination of the results from the co-key secondary endpoints of cognition (ADAS-Cog11) and function (ADCS-ADL23), which we believe is a comprehensive measure of overall disease burden.'"

P2/3 data • Alzheimer's Disease • CNS Disorders

Athira Pharma Reports First Quarter 2024 Financial Results and Pipeline and Business Updates (GlobeNewswire) - "Athira expects to report topline data from LIFT-AD in the second half of 2024....Athira expects to initiate a first-in-human study of ATH-1105 in the second quarter of 2024."

New P1 trial • P2/3 data • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies (SHAPE Trial) (clinicaltrials.gov) - P2 | N=28 | Completed | Sponsor: Athira Pharma | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Athira Pharma Announces Publication of Preclinical Data Highlighting Fosgonimeton Treatment in Models of Alzheimer’s Disease (GlobeNewswire) - "Athira Pharma, Inc...today announced the publication of preclinical data supporting the therapeutic potential of fosgonimeton in Alzheimer’s disease. The original research article…was published in the peer-reviewed journal, Neurotherapeutics....fosgonimeton treatment improved neuronal survival, protected neurite networks, and reduced tau hyperphosphorylation following Aβ injury. Fosgonimeton attenuated Aβ-induced mitochondrial stress and apoptotic signaling....Fosgonimeton improved cognitive performance in an Aβ rat model of Alzheimer’s disease....These findings bolster our confidence in the Phase 2/3 LIFT-AD trial evaluating fosgonimeton in mild-to-moderate AD, with data anticipated in the second half of 2024."

Preclinical • Alzheimer's Disease • CNS Disorders

Fosgonimeton attenuates amyloid-beta toxicity in preclinical models of Alzheimer's disease. (PubMed, Neurotherapeutics) - P2/3 | "Together, our data demonstrate the ability of fosgonimeton to counteract mechanisms of Aβ-induced toxicity. Fosgonimeton is currently in clinical trials for mild-to-moderate AD (NCT04488419; NCT04886063)."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • BECN1

Athira Pharma Presents Clinical and Preclinical Data Supporting Therapeutic Potential of Fosgonimeton in Alzheimer’s and Parkinson’s Diseases at AD/PD 2024 International Conference (GlobeNewswire) - "Athira Pharma, Inc...presented new clinical and preclinical data further highlighting the therapeutic potential of fosgonimeton at the AD/PD 2024 International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, being held in Lisbon, Portugal March 5 – 9, 2024....Athira presented an expanded dataset from the exploratory SHAPE Phase 2 clinical trial evaluating fosgonimeton in Parkinson’s disease dementia and dementia with Lewy bodies as a follow up from data shared in December 2023."

Clinical data • P2 data • Preclinical • CNS Disorders • Dementia • Lewy Body Disease • Parkinson's Disease

Athira Pharma Announces Upcoming Poster Presentation at American Academy of Neurology (AAN) 2024 Annual Meeting (GlobeNewswire) - "Athira Pharma, Inc...today announced a planned poster presentation at the upcoming American Academy of Neurology (AAN) 2024 Annual Meeting, to be held April 13 – 18, 2024, in Denver, Colorado and online. The presentation will highlight preclinical data supporting the continued development of Athira's pipeline of small molecule candidates targeting the neurotrophic hepatocyte growth factor (HGF) system, including fosgonimeton for Alzheimer’s disease, ATH-1105 for amyotrophic lateral sclerosis (ALS), and ATH-1020 for Parkinson’s disease."

Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

Targeting Neurotrophic HGF Signaling for the Treatment of Neurodegenerative Disorders (AAN 2024) - "We have developed first generation (fosgonimeton) and second generation (ATH-1020 and ATH-1105) small molecules designed to promote neurotrophic HGF system activity, with distinct properties to allow for potential therapeutic application in various neurodegenerative disorders.Design/To evaluate neurotrophic effects, primary neurons were treated with fosgonimeton, ATH-1020, or ATH-1105 and neurite outgrowth and synaptic count were measured. These results demonstrate the neurotrophic, neuroprotective, and anti-inflammatory effects of positive modulators of the HGF system. Consistent treatment effects across diverse models of neurodegenerative disorders supports the broad therapeutic potential of targeting neurotrophic HGF signaling."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • TARDBP

Hepatocyte Growth Factor and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) (EPI-LIFESTYLE 2024) - "A positive HGF/MET pathway modulator (fosgonimeton) is in Phase 2 clinical trials for mild to moderate Alzheimer’s disease...This suggests that pharmaceuticals augmenting HGF pathways may benefit in primary prevention of ICI. Confirmatory studies are needed."

Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Dementia • Fibrosis • Immunology • Infectious Disease • Inflammation • HGF